Editing Mast cell (section)

====Allergic disease====

Allergies are mediated through [[immunoglobulin E|IgE]] signaling which triggers mast cell degranulation.<ref name="MCAS 2015 review" /> Recently, IgE-independent "[[Pseudo-anaphylaxis|pseudo-allergic]]" reactions are thought to also be mediated via the MRGPRX2 receptor activation of mast cells (e.g. drugs such as [[muscle relaxants]], [[opioids]], [[Icatibant]] and [[fluoroquinolones]]).<ref>{{cite journal |vauthors=Kumar M, Duraisamy K, Chow BK |title=Unlocking the Non-IgE Mediated Pseudo-Allergic Reaction Puzzle with Mas-Related G-Protein Coupled Receptor Member X2 (MRGPRX2) |journal=Cells |volume=10 |issue=5 |pages=1033 |date=May 2021  |pmid=33925682 |doi=10.3390/cells10051033 |pmc=8146469 |doi-access=free }}</ref>

Many forms of cutaneous and mucosal [[allergy]] are mediated in large part by mast cells; they play a central role in [[asthma]], [[eczema]], [[itch]] (from various causes), [[allergic rhinitis]] and [[allergic conjunctivitis]]. [[Antihistamine]] drugs act by blocking [[histamine]] action on nerve endings. [[Cromoglicate]]-based drugs (sodium cromoglicate, nedocromil) block a calcium channel essential for mast cell degranulation, stabilizing the cell and preventing release of histamine and related mediators. [[Leukotriene antagonist]]s (such as [[montelukast]] and [[zafirlukast]]) block the action of leukotriene mediators and are being used increasingly in allergic diseases.<ref name=Prussin/>

Calcium triggers the secretion of histamine from mast cells after previous exposure to sodium fluoride. The secretory process can be divided into a fluoride-activation step and a calcium-induced secretory step. It was observed that the fluoride-activation step is accompanied by an elevation of [[cyclic adenosine monophosphate]] (cAMP) levels within the cells. The attained high levels of cAMP persist during histamine release. It was further found that catecholamines do not markedly alter the fluoride-induced histamine release. It was also confirmed that the second, but not the first, step in sodium fluoride-induced histamine secretion is inhibited by theophylline.<ref>{{cite journal |author=Alm PE |title=Sodium fluoride evoked histamine release from mast cells. A study of cyclic AMP levels and effects of catecholamines |journal=Agents and Actions |volume=13 |issue=2–3 |pages=132–7 |date=April 1983  |pmid=6191542 |doi=10.1007/bf01967316|s2cid=6977280 }}</ref> Vasodilation and increased permeability of capillaries are a result of both H1 and H2 receptor types.<ref name=pmid8151062>{{cite journal |vauthors=Dachman WD, Bedarida G, Blaschke TF, Hoffman BB |title=Histamine-induced venodilation in human beings involves both H1 and H2 receptor subtypes |journal=The Journal of Allergy and Clinical Immunology |volume=93 |issue=3 |pages=606–14 |date=March 1994  |pmid=8151062 |doi=10.1016/S0091-6749(94)70072-9|doi-access=free }}</ref>

Stimulation of histamine activates a histamine (H2)-sensitive adenylate cyclase of oxyntic cells, and there is a rapid increase in cellular [cAMP] that is involved in activation of H+ transport and other associated changes of oxyntic cells.<ref>{{cite journal |vauthors=Machen TE, Rutten MJ, Ekblad EB |title=Histamine, cAMP, and activation of piglet gastric mucosa |journal=The American Journal of Physiology |volume=242 |issue=2 |pages=G79–84 |date=February 1982  |pmid=6175225 |doi=10.1152/ajpgi.1982.242.2.G79 }}</ref>